Clinical Guidance

No genotype-phenotype correlations have been identified; however, pathogenic missense variants appear to be associated with more severe manifestations, including severe motor delay, seizures, and autism/ behavioral issues. A higher likelihood of absent speech (5/9), absent ambulation (4/9), seizures (5/9), and autistic features (5/8) were reported in individuals with MED13L pathogenic missense variants compared to other variant types . These missense variants have been located in exons 15 through 17 and exons 25 through 31. These correlations are still not completely understood and require further testing.

Source: GeneReviews — "MED13L Syndrome"

Penetrance

There are no reported individuals with a MED13L pathogenic variant that do not have manifestations of the disorder; therefore, penetrance is complete.

Source: GeneReviews — "MED13L Syndrome"

Diagnostic Criteria

Suggestive Findings

MED13L syndrome should be considered in probands with the following clinical and brain MRI findings and family history.

Clinical findings

• Mild-to-profound developmental delay

• Intellectual disability of variable degree

• Hypotonia

• Neurobehavioral manifestations

• Facial dysmorphisms. Depressed nasal bridge and bulbous nose, broad forehead, frontal bossing, up- or down-slanted palpebral fissures, large, low-set ears with prominent antihelix stem, short and deep philtrum, exaggerated Cupid's bow, macroglossia with hypotonic open mouth and/or tongue protrusion, and cleft or highly arched palate (See .)

• Musculoskeletal features, ophthalmologic involvement, congenital heart defects, and seizures in some individuals

Brain MRI findings

Source: GeneReviews — "MED13L Syndrome"

Differential Diagnosis

The phenotypic features associated with MED13L syndrome are not sufficient to diagnose this condition clinically; thus, all disorders with intellectual disability without other distinctive findings should be considered in the differential diagnosis. See OMIM Phenotypic Series for genes associated with: • Autosomal dominant intellectual developmental disorders; • Autosomal recessive intellectual developmental disorders; • Nonsyndromic X-linked intellectual developmental disorders; • Syndromic X-linked intellectual developmental disorders. Overlap in clinical features has been noted between MED13L syndrome and the disorders listed in . Table 3. Selected Disorders in the Differential Diagnosis of MED13L Syndrome

Management Guidelines

No clinical practice guidelines for MED13L syndrome have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with MED13L syndrome, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 4.

MED13L Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ special education

Neurobehavioral/

Psychiatric

| Neuropsychiatric eval | For persons age 12 mos: screening for concerns incl findings suggestive of ASD, agitation/aggression, restlessness, self-harm, tantrums, frustration, /or hyperactivity

Neurologic

| Neurologic eval | • Consider brain MRI.

• Consider EEG if seizures are a concern.

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT OT eval | To incl assessment of:

• Gross motor fine motor skills

• Radial clubhand, clubfoot, metatarsus varus, scoliosis

• Mobility, ADL, need for adaptive devices

• Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)

Eyes | Ophthalmologic eval | To assess for reduced vision, abnormal ocular movement, best corrected visual acuity, refractive errors, strabismus

Cardiovascular

| Card...

Source: GeneReviews — "MED13L Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "MED13L Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. MED13L Syndrome: Recommended Surveillance

Source: GeneReviews — "MED13L Syndrome"